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Universal physical responses to stretch in the living cell


With every beat of the heart, inflation of the lung or peristalsis of the gut, cell types of diverse function are subjected to substantial stretch. Stretch is a potent stimulus for growth, differentiation, migration, remodelling and gene expression1,2. Here, we report that in response to transient stretch the cytoskeleton fluidizes in such a way as to define a universal response class. This finding implicates mechanisms mediated not only by specific signalling intermediates, as is usually assumed, but also by non-specific actions of a slowly evolving network of physical forces. These results support the idea that the cell interior is at once a crowded chemical space3 and a fragile soft material in which the effects of biochemistry, molecular crowding and physical forces are complex and inseparable, yet conspire nonetheless to yield remarkably simple phenomenological laws. These laws seem to be both universal and primitive, and thus comprise a striking intersection between the worlds of cell biology and soft matter physics.

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Figure 1: A single transient stretch drives fractional stiffness G′ n down and the phase angle δ up, indicating fluidization of the cytoskeleton.
Figure 2: A broad variety of cell systems were fluidized by a transient stretch of 10% amplitude.
Figure 3: Two unifying relationships describe the response to stretch of a broad variety of cell systems.
Figure 4: Structural relaxation takes place on timescales that grow with the time elapsed since the application of stretch and is slower than any exponential process.


  1. Vogel, V. & Sheetz, M. Local force and geometry sensing regulate cell functions. Nature Rev. Mol. Cell Biol. 7, 265–275 (2006)

    Article  CAS  Google Scholar 

  2. Ingber, D. E. & Tensegrity, I. I. How structural networks influence cellular information processing networks. J. Cell Sci. 116, 1397–1408 (2003)

    Article  CAS  Google Scholar 

  3. Minton, A. P. How can biochemical reactions within cells differ from those in test tubes? J. Cell Sci. 119, 2863–2869 (2006)

    Article  CAS  Google Scholar 

  4. Mason, T. G. & Weitz, D. A. Linear viscoelasticity of colloidal hard sphere suspensions near the glass transition. Phys. Rev. Lett. 75, 2770–2773 (1995)

    Article  ADS  CAS  Google Scholar 

  5. Sollich, P., Lequeux, F., Hebraud, P. & Cates, M. E. Rheology of soft glassy materials. Phys. Rev. Lett. 78, 2020–2023 (1997)

    Article  ADS  CAS  Google Scholar 

  6. Cloitre, M., Borrega, R. & Leibler, L. Rheological aging and rejuvenation in microgel pastes. Phys. Rev. Lett. 85, 4819–4822 (2000)

    Article  ADS  CAS  Google Scholar 

  7. Viasnoff, V. & Lequeux, F. Rejuvenation and overaging in a colloidal glass under shear. Phys. Rev. Lett. 89, 065701 (2002)

    Article  ADS  Google Scholar 

  8. Corwin, E. I., Jaeger, H. M. & Nagel, S. R. Structural signature of jamming in granular media. Nature 435, 1075–1078 (2005)

    Article  ADS  CAS  Google Scholar 

  9. Johnson, P. A. & Jia, X. Nonlinear dynamics, granular media and dynamic earthquake triggering. Nature 437, 871–874 (2005)

    Article  ADS  CAS  Google Scholar 

  10. Matthews, B. D., Overby, D. R., Mannix, R. & Ingber, D. E. Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels. J. Cell Sci. 119, 508–518 (2006)

    Article  CAS  Google Scholar 

  11. Lau, A. W., Hoffman, B. D., Davies, A., Crocker, J. C. & Lubensky, T. C. Microrheology, stress fluctuations, and active behavior of living cells. Phys. Rev. Lett. 91, 198101 (2003)

    Article  ADS  CAS  Google Scholar 

  12. Fabry, B. et al. Scaling the microrheology of living cells. Phys. Rev. Lett. 87, 148102 (2001)

    Article  ADS  CAS  Google Scholar 

  13. Fabry, B. et al. Time scale and other invariants of integrative mechanical behavior in living cells. Phys. Rev. E 68, 041914 (2003)

    Article  ADS  Google Scholar 

  14. Alcaraz, J. et al. Microrheology of human lung epithelial cells measured by atomic force microscopy. Biophys. J. 84, 2071–2079 (2003)

    Article  ADS  CAS  Google Scholar 

  15. Trepat, X. et al. Viscoelasticity of human alveolar epithelial cells subjected to stretch. Am. J. Physiol. Lung Cell. Mol. Physiol. 287, L1025–L1034 (2004)

    Article  CAS  Google Scholar 

  16. Bursac, P. et al. Cytoskeletal remodelling and slow dynamics in the living cell. Nature Mater. 4, 557–561 (2005)

    Article  ADS  CAS  Google Scholar 

  17. Deng, L. et al. Fast and slow dynamics of the cytoskeleton. Nature Mater. 5, 636–640 (2006)

    Article  ADS  CAS  Google Scholar 

  18. Gardel, M. L. et al. Elastic behavior of cross-linked and bundled actin networks. Science 304, 1301–1305 (2004)

    Article  ADS  CAS  Google Scholar 

  19. Storm, C., Pastore, J. J., MacKintosh, F. C., Lubensky, T. C. & Janmey, P. A. Nonlinear elasticity in biological gels. Nature 435, 191–194 (2005)

    Article  ADS  CAS  Google Scholar 

  20. Fredberg, J. J. et al. Airway smooth muscle, tidal stretches, and dynamically determined contractile states. Am. J. Respir. Crit. Care Med. 156, 1752–1759 (1997)

    Article  CAS  Google Scholar 

  21. Hoffman, B. D., Massiera, G., Van Citters, K. M. & Crocker, J. C. The consensus mechanics of cultured mammalian cells. Proc. Natl Acad. Sci. USA 103, 10259–10264 (2006)

    Article  ADS  CAS  Google Scholar 

  22. Miguel, M. C. & Zapperi, S. Materials science. Fluctuations in plasticity at the microscale. Science 312, 1151–1152 (2006)

    Article  CAS  Google Scholar 

  23. Bulatov, V. V. & Argon, A. S. A stochastic-model for continuum elastoplastic behavior. 2. A study of the glass-transition and structural relaxation. Model. Simul. Mater. Sci. Eng. 2, 185–202 (1994)

    Article  ADS  Google Scholar 

  24. Brujic, J., Hermans, R. I., Walther, K. A. & Fernandez, J. M. Single-molecule force spectroscopy reveals signatures of glassy dynamics in the energy landscape of ubiquitin. Nature Phys. 2, 282–286 (2006)

    Article  ADS  CAS  Google Scholar 

  25. Moazzam, F., DeLano, F. A., Zweifach, B. W. & Schmid-Schonbein, G. W. The leukocyte response to fluid stress. Proc. Natl Acad. Sci. USA 94, 5338–5343 (1997)

    Article  ADS  CAS  Google Scholar 

  26. Yap, B. & Kamm, R. D. Mechanical deformation of neutrophils into narrow channels induces pseudopod projection and changes in biomechanical properties. J. Appl. Physiol. 98, 1930–1939 (2005)

    Article  Google Scholar 

  27. Kozlov, M. M. & Bershadsky, A. D. Processive capping by formin suggests a force-driven mechanism of actin polymerization. J. Cell Biol. 167, 1011–1017 (2004)

    Article  CAS  Google Scholar 

  28. Stamenovic, D., Suki, B., Fabry, B., Wang, N. & Fredberg, J. J. Rheology of airway smooth muscle cells is associated with cytoskeletal contractile stress. J. Appl. Physiol. 96, 1600–1605 (2004)

    Article  Google Scholar 

  29. Rosenblatt, N., Alencar, A. M., Majumdar, A., Suki, B. & Stamenovic, D. Dynamics of prestressed semiflexible polymer chains as a model of cell rheology. Phys. Rev. Lett. 97, 168101 (2006)

    Article  ADS  Google Scholar 

  30. Kirschner, M. W. & Gerhart, J. C. The Plausibility of Life: Resolving Darwin’s Dilemma (Yale Univ., New Haven, 2005)

    Google Scholar 

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These studies were supported by grants from National Institutes of Health and from the Spanish Ministries of Education and Science and Health. We thank R. Panettieri for providing cells, and R. Farré, D. Fletcher, F. Ritort and V. Viasnoff for discussions.

Author Contributions X.T. and J.J.F. designed research and wrote the manuscript. J.P.B. conducted the theoretical analysis. X.T. and D.N. designed and implemented the experimental system. X.T., L.D. and S.S.A. optimized experimental conditions and treatments. W.T.G. and D.J.T. helped to design experimental protocols and interpret data. D.J.T. provided cells and reagents. X.T. performed all stretch experiments and data analysis. J.J.F. oversaw the project.

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Correspondence to Jeffrey J. Fredberg.

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Trepat, X., Deng, L., An, S. et al. Universal physical responses to stretch in the living cell. Nature 447, 592–595 (2007).

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